Walker was born in East St. Louis, IL and went to high school there. He played minor league ball from age 17, and while he had a losing record each year from 1921 to 1925 in the minors, he was able to stay employed and in 1926 went 14-9 split between the Omaha Buffaloes and the Denver Bears. In 1927 he was 19-9 for Denver, and came up to the majors in September 1927 with the New York Giants, a team which went 92-62 that year.

Walker spent a little time in the minors with the Toledo Mud Hens in 1928, but mostly was with the big league team. He went 3-6 for the Giants although the team won 93 games under manager John McGraw. Bill then blossomed from 1931 to 1931, going 14-7, 17-15 and 16-9 as the team finished over .500 each year under McGraw. Carl Hubbell was also on the pitching staff for the Giants beginning in 1928.

Bill slipped a bit in 1932, going 8-12 for a below-.500 team, and was traded after the season to the St. Louis Cardinals who, like the Giants, had gone 72-82 in 1932. McGraw had ceased to manage the Giants as Bill Terry took over.

With the Cardinals, Bill went 9-10 the first year (1933), but had a great year for the pennant-winning 1934 tam, going 12-4 for a team which won 95 games. He was on the pitching staff with Dizzy Dean and Paul Dean and other famous pitchers also appeared in a few games - 43-year-old Dazzy Vance, 40-year-old Jesse Haines and 40-year-old Burleigh Grimes.

The book Dizzy and the Gas House Gang describes Walker as a left-hander who was the fourth starter on the team. He had a reputation as a dresser, supposedly possessing 30 tailor-made suits. He had a "chronic sore shoulder" which limited his pitching time. A different portion of the book refers to him suffering a broken arm in early May. The book Branch Rickey: Baseball's Ferocious Gentleman states that he had a broken leg that year.

Bill continued to pitch well with the Cardinals in 1935, going 13-8 for a team which won 96 games. In 1936, his ERA suffered and he was traded to the Cincinnati Reds in August, although he did not appear in the majors for them. He was in a few games for the Toronto Maple Leafs that year.